Gamma lactones



Patented Sept. 25, 1951 UNITED PATENT OFFICE GAMMA" 'LACFTONES Elbert i0. Laadaiiu Merlin P. HarveyjPa'ssaic; N. J., assignorsftofUnited StatesRubber Company, New York," N;

Jersey Y5, a corporation of New No Drawing. Applicatih'ii Apriiw, 1949, Serial No. 88,488

novel method of preparing thesame'. More "specifically the invention relates to the preparation of such lactones having the formula OC-CX2CH2CRR" from 2,2,4 trihalogenoalkanoic"esters of th eral formula RO CO CX2- CH.2 CXR,R

wherein each 'Xis one ofthe halogen atoms chlorine or bromine; R is 'a lower alkyl group (e. g., methyl, ethyl, propyl) and R and Rfmay be one of the radicals hydrogen and lower alkyl (e. g., methyl, ethyl and prom/1).

The 2,2,4-triha1ogenoalkanoic esters which are the starting materials for use, in our invention can themselves be readily prepared by heating at 25420 a delta 1 '01efin that a monoole" r ma-lactones can be modified by suitable reactions finic hydrocarbon, having a terminal methylene group and being of the type CH2 CRR", where in R. and R. are as previously defined, with from 1 to 20 molar equivalents of a trihalogeno 'acetic acid ester RO-COCX3, wherein R and Kara as previously defined, in the presence of a source of free radicals, e. g., a peroxidiccomp'ound, such as benzoyl peroxide' This is illustrated by re action (1') below:

V iree radicals ROCOOX3 nCHg=ORI n n beingxa small integer; e. g., 1-5. Those prod-' ucts of the above formula in which 71:1 are those employed in'our invention.

The method of ourinvention consists in heating such a 2,2,4-trihalogenoalkanoicester starting material at from 25 C. to 150 C. for from-1 to 24 hours and advantageously with a catalytic ric chloride; the latter being preferred.- The re'-" (c1. zen-344i action is carried out in the presence or absence of an inert diluent: The reaction ofour inven-- traction, fractional distillation and/or crystalli- 1 zation.

We have found that despite the well-known lability of the alpha-halogen atoms in alphaso, the resulting alpha, alpha-dihalogeno-gaminvolving the alpha-halogeii'atomor atoms, such I as hydrolysis, 'alkylation and dehydro halogena tion. -Hencetheselactones-provideintermediates for the synthesis of a wide variety of organiccompounds and they find particular" use in the i preparation of pharmaceuticals.

The following example discloses our invention in more detail. All parts are by weight.

Example The starting material used in this eirample was prepared as follows:

A mixture of 1150 parts of ethyl trichloroacetate, 1-06 parts of isobutylene and 14.5 parts of benzoyl peroxide is heated-with agitation in 'a '35' pressure vessel at 70 C. for 48hours. The re-' actionmixture" is fractionally distilled to yield 206 parts of the new compoundeth'yl' 2,2,4-tri- -n 1.4688; chlorine content, 42.68% (theory, "42.97%) V A portion (123.69 partsf'of'theethyl 2,2,4-tri- '45 for 12 hours, during which ethyl chloride is 3 formed as a by-product." The reaction mixture is then cooledtoroom temperature and it solidi} fies upon standing. The crude'lactone' of 2,2?di

chlorol-methyll-hydroxypentanoic' acid, upon 50 recrystallization from n-hexane', melts'at 5635- The products can be isolated and purified by ex-I H halogenoalkanoic acids, -esters,'-etc., the alpha a halogen atom of our starting material-does not participate in the-reaction of our'invention; parv ticularly where R and/or R" are alkyl groups,"

"chloro-4-methylpentanoate, b. 813 C./2 mm:

3 tion which yields 52.6 parts of this new lactone, m. 58-9 C.; chlorine content, 38.39% (theory,

In a similar manner the following reactlons are carried out:

radicals Any 2,2,4-trihalogenoalkanoic ester may be converted to the corresponding gamma-lactone by means of our invention. Examples are:

Having thus described our invention, what we claim and desire to protect by Letters Patent is:

1. As a new chemical, a lactone having the formula OCCXz-CH2CR'R" where X is one of the halogens chlorine and bromine, and R and R are radicals of the class consisting of hydrogen and lower alkyl.

2. As a new chemical compound, a lactone having the formula 3. The method which comprises heating a 2,2,4- trihalogenoalkanoic ester of the formula where X is one of the halogens chlorine and bromine, R is a lower alkyl group and R and R" are radicals of the class consisting of hydrogen and lower alkyl under anhydrous conditions, and thereby converting said ester to a lactone having the formula wherein X, R and R" all are as before.

4. The method which comprises heating a 2,2,4-trihalogenoalkanoic ester of the formula where X is one of the halogens chlorine and bromine, R is a lower alkyl group and R and R" are radicals of the class consisting of hydrogen and lower alkyl in the presence of a catalytic amount of an anhydrou acidic catalyst selected.

4 from the group consisting of sulfuric acid, ptoluenesulfonic acid and polyvalent metal halides of the Friedel and Crafts type and at a temperature of from 25 C. to 150 C., and thereby converting said ester to a lactone having the formula wherein X, R and R" all are as before.

5. The method which comprises heating a 2,2,4- trihalogenoalkanoic ester of the formula where X is one of the halogens chlorine and bromine, R is a lower alkyl group and R and R are radicals of the class consisting of hydrogen and lower alkyl in the presence of anhydrous ferric chloride in an amount ranging from 0.05 to 5.0% by weight based on said ester and at a temperature of from 25 C. to 150 C., and thereby converting said ester to a lactone having the formula wherein X, R and R all ar as before.

6. The method of making the gamma-lactone of 2,2 dichloro 4-methyl-4-hydroxypentanoic acid which comprises heating ethyl 2,2,4-trichloro-4-methy1pentanoate under anhydrous conditions at a temperature at which it decomposes and thereby forming the gamma lactone of 2,2-dichloro-4-methyl 4 hydroxypentanoic acid and ethyl chloride.

' 7. The method of making the gamma-lactone of 2,2-dichloro-4-methyl 4 hydroxypentanoic acid which comprises heating ethyl 2,2,4-trichloro-4-methylpentanoate in the presence of a catalytic amount of an anhydrous acidic catalyst selected from the group consisting of sulfuric acid, p-toluenesulfonic acid and polyvalent metal halides of the Friedel and Crafts type at a temperature of from 25 C. to 150 C., and thereby converting said ethyl 2,2,4-trichloro-4-methylpentanoate to the gamma lactone of 2,2-dichloro- 4-methyl-4-hydroxypentanoic acid.

8. The method of making the gamma-lactone of 2,2-dichloro-4-methyl 4 hydroxypentanoic acid which comprises heating ethyl 2,2,4-trichloro-4-methy1pentanoate at a temperature of from 25 C. to 150 C. in the presence of anhydrous ferric chloride in an amount ranging from 0.05 to 5.0% by weight based on said ethyl 2,2,4- trichloro-4-methylpentanoate.

9. The method of making the gamma-lactone of 2,2-dichloro-4-methyl 4 hydroxypentanoic acid which comprises heating ethyl 2,2,4-trichloro-4-methylpentanoate at a temperature of C. in the presence of anhydrous ferric chloride in an amount ranging from 0.05 to 5.0% by weight based on said ethyl 2,2,4-trichloro-4- methylpentanoate and recovering th gammalactone of 2,2-dichloro-4-methyl 4 hydroxy- 1pentanoic acid from the resulting reaction mixure.

ELBERT C. LADD. MERLIN P. HARVEY.

REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date ,526 Elderfield Dec. 11, 1945 2. 81 0 add et a1. ".2---" Oct. 18, 1949 

1. AS A NEW CHEMICAL, A LACTONE HAVING THE FORMULA 